The principal objective of this research program is to gain an understanding of genetic control mechanisms which underly the expression of enzymes in animal cells. This objective is being pursued by genetic and biochemical analyses of mutations which alter the expression of murine glucuronidase. Glucuronidases from high and low activity strains exhibit a difference in structure as determined by heat sensitivity. Genetic studies suggest that the control of the differences in activity level as well as the difference in structure resides in an element in close proximity to, or identical with, the glucuronidase structural gene. The difference in tissue activity levels between high and low activity strains is a function of the rate of synthesis of glucuronidase. Proposed work includes a detailed analysis of the genetic element(s) controlling the structure and rate of synthesis of glucuronidase and characterization of the structural difference between the glucuronidases of mutant and normal strains of mice. BIBLIOGRAPHIC REFERENCES: Smith, K., and Ganschow, R. E. (1975) The turnover of two subcellular forms of an acid hydrolase. J. Cell. Biol. 67:407a. Elangovan, S., and Ganschow, R. E. (1976) Purification of murine Beta-glucuronidase by immunoaffinity chromatography. Fed. Proc. 35:1550.